Local anesthetics are generally used for suppressing nociceptive pains and administered by local injection in general. The pharmaceutical composition for local injection generally contains a local anesthetic with concentration of 0.2 to 2%. In recent years, due to the reasons like a change in risk and benefit balance that is caused by standardization of anti-coagulation therapy after surgery or less invasive surgery, a situation has arrived in which epidural anesthesia, considered to be a gold standard up until now, cannot be the first choice for pain relief after surgery.
Opioid IV-PCA, peripheral nerve blocking, and combinations thereof are mainly used at present moment as a replacement method for epidural anesthesia. However, whereas the pain relieving effect after surgery is required for 1 to 3 days or so, the duration of effect of the peripheral nerve blocking based on injection of a local anesthetic is as short as a half day.
In recent years, a gelated local anesthetic agent containing local anesthetics has been suggested.
For example, disclosed in JP 2011-508788 W (Patent Literature 1) is a plurality of embedded type pharmaceutical depot preparation useful for alleviating, preventing, or treating pains and/or inflammations of a patient who is in need of the treatment in which the preparation contains at least one pharmaceutical depot preparation of a first set that can release, in an area under skin, a therapeutically effective bolus amount of pain reliever and/or anti-inflammation pharmaceutical, or pharmaceutically acceptable salts thereof, and at least one pharmaceutical depot preparation of a second set that can release for a period of at least 3 days a therapeutically effective amount of pain reliever and/or anti-inflammation pharmaceutical, or pharmaceutically acceptable salts thereof.
Furthermore, disclosed in JP 2013-523693 W (Patent Literature 2) is a thermally gelated and stabilized pharmaceutical composition of at least one local anesthetic, in which the composition has pH close to pKa of the local anesthetic and contains (a) base form of one or more kinds of local anesthetics (ATC code: NO1BB) of an amide type, (b) 10 to 30% by weight of polyoxyethylene castor oil, and (c) at least 15% by weight of one or more of surfactants for giving the thermal gelation property to the composition.
Furthermore, disclosed in JP 2013-523694 W (Patent Literature 3) is a stabilized and gelated aqueous bioadhesive pharmaceutical composition which contains (a) one or more kinds of local anesthetics in an anesthetically effective amount, (b) monoglyceride or diglyceride, or a mixture of long chain fatty acid thereof in an amount of 15 to 70% by weight, and (c) free long chain saturated or unsaturated fatty acid in an amount of 5 to 60% by weight, and has a behavior of an anisotropic organic phase which enables swelling in an administration area containing excessive moisture.
Furthermore, it has been found by the applicant of the present application that an aqueous solution containing glycyrrhizic acid at low concentration and a cationic substance can form a matrix (i.e., hydrogel), and suggested WO 2012/102210 A (Patent Literature 4) in which a gel composition containing a complex of (1) glycyrrhizic acid and a cationic substance is described.